CLINICAL TRIALS AND THERAPEUTICS Treatment of osteoarthritis with aspartame

Background: The binding of sweet-tasting compounds in a human (Meg) BenceJones dimer has been characterized by x-ray crystallography. Aspartame binding in this immunoglobulin fragment is remarkable. Unexpected pain relief noted by A.B.E., a crystallographer with diagnosed osteoarthritis, suggested that the accommodation of aspartame in the active site of the dimer may represent surrogate binding by other proteins, with analgesia as the outcome. Methods: X-ray analysis of the complex of aspartame and the Bence-Jones dimer was conducted with crystalline Meg protein and pure aspartame. A single-blind (n = 1) study to confirm analgesia was completed by administration of aspartame to A.B.E. A controlled double-blind trial was performed in patients with x-ray-documented osteoarthritis. Pain and performance changes were evaluated with use of two doses of placebo and two doses of aspartame. Effects on bleeding time were then evaluated by determination of template bleeding times in 34 normal volunteers. Finally, antipyretic effects were studied in SpragueDawley rats given intramuscular turpentine injections. Results: Aspartame binding in the BenceJones dimer was verified by x-ray crystallography. Improvements in performance and pain relief were observed in A.B.E. at p < 0.001. Decreased pain and improved performance were also observed in patients with osteoarthritis (p < 0.001). Mild antihemostatic responses were observed in bleeding times after aspartame treatment. Modified template bleeding times increased at p < 0.01. Aspartame blocked the turpentine-mediated febrile rsponses in the treated rats (p < 0.01). Concl~ions: L-Aspartyl-L-phenylalanine methyl ester is biologically active and appears to relieve pain, induce mild antithrombotic effects in humans, and decreas e fever in animals. (Clin Pharmacol Ther 1998;63:580-93.)